Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21–29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.     

The predictive factors of low serum 25-hydroxyvitamin D and vitamin D deficiency in patients with systemic lupus erythematosus

Vitamin D is a steroid hormone with pleiotropic effects. The association between serum 25-hydroxyvitamin D level [25(OH) D] and lupus nephritis are not clearly known. We aim to determine serum 25(OH) D levels in patients with inactive SLE, active SLE without lupus nephritis (LN) and active SLE with LN and to identify clinical predictor of vitamin D deficiency. One hundred and eight SLE patients were included. Patients were classified as Group (Gr) 1, 2 and 3 if they had SLE disease activity index (SLEDAI) <3, ≥3 but no LN and ≥3 with LN. Important baseline characteristics were collected. 25(OH) D was measured by high performance liquid chromatography (HPLC). SLEDAI in Gr1, Gr2 and Gr3 was 0.7 (0.9), 5.6 (2.3) and 9.2 (5.2), respectively. 43.5 % had vitamin D insufficiency and 29.6 % had vitamin D deficiency. Mean 25(OH) D in each groups was 28.3 (8.0), 26.7 (9.5) and 19.9 (7.6) ng/ml (p < 0.001 comparing Gr1 and 3) (p = 0.003 comparing Gr2 and 3). Vitamin D deficiency was found in 11.1, 22.2 and 55.6 % of Gr1, 2 and 3. Linear regression analysis found that 25(OH) D was significantly correlated with serum albumin (r = 0.28, p = 0.004), inversely correlated with SLEDAI (r = ?0.22, p = 0.03) and urinary protein creatinine index (UPCI) (r = ?0.28, p = 0.005), but not with sun exposure score, body mass index and estimated GFR. Only UPCI was significantly inversely correlated with 25(OH) D (p = 0.02) from multiple linear regression. LN was a significant predictor of vitamin D deficiency from multivariate logistic regression (OR 5.97; p = 0.006). Vitamin D deficiency and insufficiency was found in 93 and 86 % of LN with proteinuria ≥ and <500 mg/day. We conclude that SLE patients with LN have significantly lower vitamin D level than inactive SLE and active SLE without LN. Hence, nephritis is a significant predictor of vitamin D deficiency in SLE patients.     

Vitamin D deficiency is associated with digital ulcer but not with atherosclerosis or arterial stiffness in patients with systemic sclerosis: a pilot study

The objective of this study was to investigate the association of vitamin D deficiency with digital ulcers (DUs) that result from microvasculopathy, carotid intima-media thickness (CIMT) as surrogate markers of atherosclerosis, and brachial-ankle pulse wave velocity (baPWV) representing arterial stiffness in patients with systemic sclerosis (SSc). In this cross-sectional study, 40 female SSc patients and 80 healthy controls matched for sex, age, and blood sampling season were recruited. Vitamin D deficiency was defined as serum 25-OHD levels <30 ng/mL. “DUs ever” included active and healed DUs. CIMT and carotid plaque were examined using high-resolution ultrasonography, and baPWV was measured using an automatic waveform analyzer. Vitamin D deficiency was more prevalent in SSc patients than in controls (30 vs. 11.3%). Regarding SSc patients, 9 (22.5%) had DUs ever, and the mean CIMT and baPWV were 0.68 mm and 1561.1 cm/s, respectively; carotid plaque was detected in 13 (34.2%) patients. The frequency of DUs ever was significantly higher for SSc patients with vitamin D deficiency than those without this feature (50 vs. 10.7%, p = 0.012), but the median CIMT and baPWV and the frequency of carotid plaque did not differ according to the presence of vitamin D deficiency. Multivariable logistic regression analysis showed that vitamin D deficiency was an independent risk factor for DUs ever (OR = 7.72, p = 0.024). Vitamin D deficiency was associated with DUs, but not with atherosclerosis or arterial stiffness, potentially indicating that vitamin D may have different effects on the microvascular and macrovascular involvement in SSc pathophysiology.     

Macrophage activation syndrome in children with systemic juvenile idiopathic arthritis and systemic lupus erythematosus

Macrophage activation syndrome (MAS) is a hyper-inflammatory disorder secondary to a rheumatic disease such as systemic juvenile idiopathic arthritis (SJIA) and systemic lupus erythematosus (SLE). We aimed to present the characteristics of our pediatric MAS patients. Clinical features, laboratory parameters, treatment, and outcome of 34 patients (28 SJIA; six SLE; 37 MAS episodes) followed at a tertiary health center between 2009 and 2015 were retrospectively reviewed. The median age at MAS onset was 11 years. More SJIA patients had MAS at disease onset than SLE patients (53.6 vs. 16.7 %). Fever, high C-reactive protein and hyperferritinemia were present in all MAS episodes. Rash was less (p = 0.03), and fatigue was more frequent (p = 0.042) in SLE than SJIA patients. All received corticosteroids. Cyclosporine was given in 74.2 % of SJIA-MAS; 66.7 % of SLE-MAS episodes. Intravenous immunoglobulin, anakinra, or etoposide was administered during 67.7; 41.9; 32.3 % of SJIA-MAS and 33.3; 33.3; 50 % of SLE-MAS episodes, respectively. Plasmapheresis was performed during 41.9 % of SJIA-MAS and 33.3 % of SLE-MAS episodes. The mortality rate was 11.8 % (n = 4;3 SJIA, 1 SLE). Hepatosplenomegaly was more frequent (p = 0.005), and plasmapheresis was performed more frequently (p = 0.021) in the patients who died compared to the cured patients. The median duration between symptom onset and admission to our hospital was longer among the patients who died (16.5 vs. 7 days; p = 0.049). Our patients’ characteristics were similar to the reported cases, but our mortality rate is slightly higher probably due to late referral to our center. Early diagnosis and effective treatment are crucial to prevent mortality.     

Vitamin A improve Th17 and Treg regulation in systemic lupus erythematosus

The aim of this study was to determine the role of vitamin A in modulating T helper 17 (Th17) and regulatory T cell (Treg) balance in systemic lupus erythematosus (SLE) patients. Sixty-two female SLE patients and sixty-two female controls were measured for vitamin A levels from serum by enzyme-linked immunosorbent assay (ELISA) and percentages of Th17 and Treg from peripheral blood mononuclear cells (PBMC) by flow cytometry. We also performed an in vitro study to evaluate the effects of retinoic acid treatment (0, 0.1, 0.2, and 0.3 μg/ml) in modulating Th17/Treg balance in CD4⁺ T cell culture from hypovitaminosis A SLE patients. Th17 and Treg percentages from cell cultures were measured by flow cytometry. Vitamin A levels in the SLE patients were lower compared to those in the healthy control (46.9?±?43.4 vs. 75.6?±?73.1 ng/ml, p?=?0.015). Vitamin A levels also had a negative correlation to Th17 percentages in the SLE patients (p?=?0.000, R?=??0.642). Th17 percentages in the hypovitaminosis A SLE patients were higher compared to those SLE patients with normal vitamin A levels (10.9?±?5.3 vs. 2.9?±?2.2 %, p?=?0.000). Treatment of 0.3 μg/ml of retinoic acid could increase Treg differentiation (33.9?±?1.6 vs. 21.8?±?1.1 %, p?=?0.000) and decrease Th17 differentiation (27.2?±?2.5 vs. 37.4?±?1.3 %, p?=?0.000). In conclusion, vitamin A has important roles in modulating Th17/Treg balance in the SLE patients shown by the significant decrease of vitamin A levels in the SLE patients which negatively correlate with Th17 population, and treatment of retinoic acid could decrease Th17 and increase Treg percentages in CD4⁺ T cells cultures.     

Vitamin D deficiency as a risk factor for the development of autoantibodies in patients with ASIA and silicone breast implants: a cohort study and review of the literature

The development of autoimmunity and/or autoimmune diseases is multifactorial. Vitamin D is one of the factors that might play a role. We postulated that both the presence of adjuvants and insufficient levels of vitamin D may result in the development of autoimmunity in patients with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in relation to silicone implant incompatibility. We measured vitamin D levels in 135 patients with ASIA in relation to silicone implant incompatibility and related findings to the presence of autoantibodies that are commonly used to diagnose systemic autoimmune diseases. Furthermore, we systematically reviewed the literature regarding vitamin D deficiency as a risk factor for the development of autoantibodies. Vitamin D measurements were available for analysis in 131 of 135 patients with ASIA in relation to SIIS. Twenty-three patients (18%) tested positive for autoantibodies, from which 18 patients (78%) had either a vitamin D deficiency or insufficiency (median vitamin D level 60.5 mmol/L), whereas five patients (22%) had sufficient vitamin D levels. The risk to develop autoantibodies was significantly increased in vitamin D deficient and/or insufficient patients [RR 3.14; 95% CI, 1.24–7.95; p = 0.009]. Reviewed literature suggested an association between vitamin D levels and the presence and/or titer levels of autoantibodies in different autoimmune diseases. From our current study and from our review of the literature, we conclude that vitamin D deficiency is related to the presence of autoantibodies. Whether vitamin D supplementation results in a decrease of autoimmunity needs to be studied prospectively.     

Vitamin D Receptor (VDR) Gene Polymorphisms (<Emphasis Type="Italic">Fok</Emphasis>I, <Emphasis Type="Italic">Bsm</Emphasis>I) and their Relation to Vitamin D Status in Pediatrics βeta Thalassemia Major

Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked Immunosorbent Assay [ELISA], VDR (FokI, BsmI) gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR–RFLP].Serum levels of calcium, phosphorus, alkaline phosphatase and ferritin were determined in 50 Pediatrics beta thalassemia major patients and 60 controls. Patients had significantly lower serum calcium (p < 0.001) lower serum vitamin D3 (p < 0.001) with elevated levels of phosphorus (p < 0.001) and alkaline phosphatase than controls (p = 0.04). Of the patients studied, 60 % had vitamin D deficiency (<20 ng/ml), 20 % had vitamin D insufficiency (21–30 ng/ml) and 20 % had sufficient vitamin D status (>30 ng/ml). Patients harboring mutant (Ff,ff) and wild (BB) genotypes were associated with lower serum calcium (p = 0.08, 0.02) respectively, lower vitamin D3 levels (p < 0.001, 0.01) respectively. They were also suffering from more bony complications although the difference was not statistically significant (p > 0.05). In conclusion, these results suggest that the VDR (FokI, BsmI) gene polymorphisms influence vitamin D status, (Ff,ff), BB genotypes had lower vitamin D levels, so they might influence risk of development of bone diseases in beta thalassemia major.     

Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature

Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease’s features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (≥30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = ?0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level ≥30 ng/ml (8/15 vs. 6/34; p = 0.017). In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.     

Effect of vitamin D level on the immunogenicity to hepatitis B vaccination in dialysis patients

We undertook this study to assess the response of hepatitis B vaccination in dialysis patients and the effect of vitamin D level on the immunogenicity to hepatitis B vaccination. It was an observational study, which included 60 patients of end-stage renal disease on maintenance dialysis. Patients with anti-HBs antibody positive at baseline were excluded. All received intramuscular recombinant hepatitis B vaccination at 0, 1, 2, and 6 months 20 μg on each deltoid muscle bilateral. Anti-HBs antibody titers were measured at 4 and 7 months of vaccination and the titer ≥10 mIU/mL was considered as “positive”. Vitamin D levels were measured at baseline before starting the vaccination. The mean vitamin D level was 15.0?±?7.8 ng/mL. The vitamin D level <10 and <20 were 23.3% and 83.3 %, respectively. The patients on hemodialysis had relatively higher vitamin D level than on peritoneal dialysis patients, i.e. 16.3?±?8.5 and 11.5?±?3.1 ng/mL, respectively (p?=?0.03). Overall, 38 patients responded to the immunization (63.3 %) and 11 patients were non-responders (36.7 %) at 4 months. Difference of vitamin D level in responder (16.6?±?9.1 ng/mL) and non-responder (12.4?±?4.1 ng/mL) was not significant (p?=?0.16). At 7 months (1 month after completion of vaccination) 61.9 % were responders and 38.1 % were non-responders. The vitamin D level in responders and non-responders were statistically not significant (p?=?0.11). In responder, titer ≥100 mIU/mL was seen in 30 % at 4 months and in 42.9 % at 7 months (p?=?0.05). In the good and weak responders at 7 months, vitamin D levels were 21.5?±?10.8 and 10.1?±?3.7 ng/mL, respectively (p?=?0.37). The association of vitamin D level and anti-HBs antibody titer were not significant (r?=?0.03 and 95 % CI was ?0.43 to 0.48, p?=?0.89) in those who responded. Most patients on dialysis were vitamin D deficient. Vitamin D levels did not differ between responding and non-responding dialysis patients.     

Vitamin D Deficiency Is Associated with Ulcerative Colitis Disease Activity

Purpose

Previous studies on experimental mouse models have suggested a role of vitamin D in immune system regulation and IBD disease severity. In this study, we examine the relationship between vitamin D levels and clinical disease activity in human subjects with ulcerative colitis (UC). We hypothesized that patients with vitamin D deficiency will display increased UC disease activity as compared to patients with normal vitamin D levels.

Methods

A cross-sectional study was performed by querying the outpatient electronic medical record of our health system for patients seen in the gastroenterology clinic from January 2007 to October 2009 who carried both a diagnosis of UC and a documented 25-OH vitamin D level within 30 days of their clinic visit. Demographic and clinical variables were collected. Clinical disease activity was calculated using the six-point partial Mayo index. Active disease was defined as a six-point index score of ≥1. Vitamin D deficiency was defined as a 25-OH D level below 30 ng/ml. Data were analyzed using the chi-square distribution test.

Results

Thirty-four patients met inclusion criteria (53 % female, mean age 45.7 ± 24.7 years). Fifteen patients had normal vitamin D levels and 19 patients were vitamin D deficient. Twelve patients had vitamin D levels <20 ng/ml. Vitamin D deficient patients were statistically more likely to have increased disease activity than patients with normal vitamin D levels (p = 0.04), with 68 % of deficient patients displaying active disease compared with 33 % in the sufficient group. There was also a statistically significant association between vitamin D status and need for treatment with steroids, with a higher percentage of vitamin D deficient patients (47 %) requiring such treatment compared with 7 % in the sufficient group (p = 0.02). There was no association between season of visit and disease activity.

Conclusion

Vitamin D deficiency is common among patients with active UC, particularly those requiring corticosteroids. Further investigation is needed to determine the clinical utility of vitamin D monitoring in patients with UC and whether there is a role for vitamin D as a treatment for UC.     

<Emphasis Type="Italic">C-reactive protein</Emphasis> +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels

The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068–2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410–9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299–2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.     

Vitamin D Deficiency and Its Association with Inflammatory Markers,Lipid Profile and Regulatory T-cells in Pediatric Sickle Cell Disease Patients

We investigated vitamin D deficiency in pediatric sickle cell disease patients and its association with selected bone, lipid and inflammatory parameters. The study included 64 patients (33 SS and 31 SB) and 21 carriers (AS). Blood was obtained to assess levels of vitamin D, WBC, CRP, Ca, P, ALP, PTH, triglyceride, total cholesterol, LDL, VLDL, HDL, IL-2, IL-12, TNF-α, IL-4, IL-6, IL-10 and regulatory T cells. The patients were grouped according to their genotype (SS, SB) and vitamin D status (low or normal). Carriers were also grouped as low or normal vitamin D. Laboratory findings were similar between low and normal Vit D groups in SS, SB and AS genotypes except a lower IL-12 in SB-low vitamin D compared SB-normal vitamin D group. Acute chest syndrome was more frequent in SS-low Vit D (63%) compared to SS-normal Vit D (25%), SB-low Vit D (21%) and SB-normal Vit D (33%) (P = 0.045). Both SS and SB with low vitamin D had higher VLDL (P = 0.006 and P = 0.022), TNF-α (P = 0.001) and regulatory T cells (P = 0.000) compared to AS-low vitamin D. Both SS and SB with normal vitamin D had higher levels of regulatory T cells (P = 0.000) compared to AS-normal vitamin D. Vit D was not a modifier of selected inflammation, bone and lipid parameters in sickle cell disease. Acute chest syndrome was comparably more frequent in SS-low vitamin D. Increase of regulatory T cells in the patients was a result of chronic inflammation in sickle cell disease.     

Heart involvement in systemic lupus erythematosus: a systemic review and meta-analysis

Cardiovascular diseases are one of the most important causes of the disability and mortality in patients with systemic lupus erythematosus (SLE). The present study examined the cardiac abnormalities in patients with SLE by echocardiography. Case-control studies were obtained by searching PubMed MEDLINE, Embase, and MD Consult. Systemic review and meta-analysis were performed to assess the cardiac abnormalities based on the changes in the echocardiography in patients with SLE. Twenty-two studies including 1117 SLE patients and 901 healthy controls were enrolled into this study. We found that patients with SLE developed the pericardial effusion (odds ratio (OR) (95 % confidence interval (CI)) 30.52 (9.70–96.02); p < 0.00001) and the combined valvular alterations (OR (95 %CI) 11.08 (6.98–17.59); p < 0.00001). In addition, SLE patients also exhibited an increase in the left atrial diameter (LAD) (WMD—weighted mean difference (95 %CI) 0.18 (0.06–0.29); p = 0.002), the left ventricular internal diameter in diastole (LVDd) (WMD (95 %CI) 0.07 (0.02–0.12); p = 0.01), and the left ventricular mass index (LVMI) (WMD (95 %CI) 5.69 (2.69–8.69); p = 0.0002). In contrast, the left ventricular systolic function (WMD (95 %CI) ?1.22 (?1.69 to ?0.75); p < 0.00001) and diastolic function including E/A ratio and E/E’ ratio (WMD (95  % CI) ?0.13 (?0.24 to ?0.01); p = 0.04; WMD (95  % CI) 1.71 (0.43 to 2.99); p = 0.009) were decreased in SLE patients. Patients with SLE are associated with significant alterations in cardiac structure and function as demonstrated by echocardiography. Data from this study suggest that echocardiographic assessment should be considered as a part of routine examinations for SLE patients clinically.     

Vitamin D deficiency and the associated factors in children with type 1 diabetes mellitus in southern Iran

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder caused by destruction of beta cells of the pancreas. Several reports have suggested a connection between vitamin D deficiency and T1DM and the possible role of dietary vitamin D supplementation in reducing the risk of T1DM. There is little knowledge about the prevalence of vitamin D deficiency among Iranian children with T1DM. Serum 25-hydroxy vitamin D (25OHD) was assayed by high performance liquid chromatography in 8–18-year-old diabetic patients referred to pediatric diabetes clinics in Shiraz, Iran, during a period of 14 months. The age of the onset of T1DM, daily insulin usage, weight, height, and BMI of each patient were recorded along with levels of physical activity and sun exposure. The patients’ body composition was determined by DEXA and used in further analysis. This study was conducted on 39 diabetic boys and 46 diabetic girls aged 12.4 ± 4.2 years. Mean serum 25(OH)D3 was 18 ± 12.2 ng/dl. Serum levels of 25(OH)D3 were higher in boys than girls. 7.7 % of the boys and 30.4 % of the girls had severe vitamin D deficiency. There was a negative correlation between the age of the onset of T1DM and serum concentration of 25(OH)D3 (p = 0.006, r = ?0.17). Girls with T1DM showed a higher prevalence of severe vitamin D deficiency than boys with T1DM. Moreover, vitamin D deficiency was more prevalent in individuals with earlier onset of the disease and in those with higher fat mass index.     

Association between paraoxonase-1 gene Q192R and L55M polymorphisms in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) in a population from Cairo of Egypt

Paraoxonase-1 (PON1) is involved in the oxidative stress process that cause tissue damage observed in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). The aim of the present study was to investigate the association of PON1 Q192R and L55M polymorphisms with risk of SLE and associated APS among Egyptian sample. The study included 120 SLE patients (45 without APS and 75 with APS) and 120 healthy subjects. PON1 Q192R and L55M polymorphisms were genotyped by real-time PCR. No significant differences in Q192R genotypes or allele frequencies were found between patients and controls (p = 0.5 and 0.1, respectively). The frequency of the 55M allele was significantly higher in SLE patients than in controls (66.6 vs. 43.3%), while the 55L allele was more frequent in controls (56.6%) than in patients (33.3%) (p = 0.03). The LL genotype was more frequent in controls (21.6%) than in patients (10%) while M allele carrier genotypes (LM + MM) were more frequent among patients (90%) than controls (78.3%), p = 0.04. Also, the 55M allele was more frequent in APS patients (73.3%) than in patients without APS (55.6%), p = 0.004. M allele carrier genotypes (LM + MM) was significantly higher among APS patients (95.4%) than in non-APS patients (80%), p = 0.008. Our results indicated that the PON1 L55M polymorphism associated with SLE and associated APS in a population from Cairo of Egypt, while the Q192R polymorphism plays no role in disease susceptibility. A large scale study to assess PON1 polymorphisms, PON1 activity, and markers of oxidative stress interaction is needed to clarify the role of PON-1 polymorphisms in the pathogenesis of SLE and associated APS.     

Age of onset influences on clinical and laboratory profile of patients with systemic lupus erythematosus

The present study aims to evaluate differences in clinical and laboratory manifestations and medication use in the different ages of disease onset in patients with systemic lupus erythematosus (SLE). This cross-sectional study consisted of 598 SLE patients (550 female and 48 male), who attended the Rheumatology Clinic of the Hospital de Clínicas de Porto Alegre between 2003 and 2015. Demographic, clinical and laboratory data were collected. The patients were classified into three groups according to their ages at disease diagnosis. Mean age of diagnosis was 33.6 ± 14.3 years, and the median (25th–75th percentile) disease duration was 13 (7–20) years. Among the patients studied, 419 (70%) were adult-onset (aSLE), 90 (14.8%) were late-onset (lSLE) and 89 (14.8%) were childhood-onset (cSLE). The female to male ratio was higher in aSLE (18:1) compared to the other groups (p = 0.001). Arthritis was predominantly found in aSLE (78.5%) when compared with lSLE (57.7%) (p < 0.001). Nephritis was more common in cSLE (60.6%) than in lSLE (26.6%) (p < 0.001). Median (25th–75th percentile) of SLE disease activity index (SLEDAI) was higher in the cSLE group [2 (0–5)] when compared to the lSLE group [0 (0–4)] (p = 0.045). Childhood-onset SLE showed a more severe disease due to the higher incidence of nephritis and needed a more aggressive treatment with immunosuppressive drugs.     

Effect of vitamin D supplementation on reduction of cardiometabolic risk in patients with type 2 diabetes mellitus and dyslipidemia

Endothelial progenitor cells (EPCs) participate in endothelial regeneration. Previous studies link vitamin D deficiency, inflammatory cytokines, and cardiovascular disease (CVD) risk. This study evaluates the impact of vitamin D supplementation on EPCs, inflammatory markers, and glycemia in type 2 diabetes. This is prospective open-label randomized controlled study. Sixty-five patients with type 2 diabetes, dyslipidemia, HbA_1c below 9%, and vitamin D deficiency (below 30 ng/ml) attending the outpatient clinic between April and December 2015 were randomized to active vitamin D (60,000 IU of vitamin D orally once a week for 8 weeks, followed by once a month for 4 months) or control for 6 months. Data was analyzed with STATA 14. Demographics include median age 54 (range 48.5–60) years, median duration of diabetes 7 (4–12.5) years, mean BMI 26.86 ± 3.8 kg/m², mean HbA_1c 7.22±0.8%, and median vitamin D 13.42 (range 10.24–17.23) ng/ml; 50% were men. Vitamin D supplementation increased vitamin D levels in the active group compared to control (p < 0.01). EPCs decreased in both groups from baseline. There was no difference in change in EPCs, hsCRP, IL-6, IL-10, TNF-α, and HbA_1c or insulin resistance (HOMA-IR) between the active- and control-groups at the end of the study. Vitamin D supplementation did not alter EPCs or inflammatory markers, or improve glycemic control at the dose and duration investigated. Further studies are needed to study the long-term effects on markers of endothelial repair.     

The effects of long- and short-term interdisciplinary treatment approaches in women with fibromyalgia: a randomized controlled trial

We investigated the effects of long- and short-term interdisciplinary treatment approaches for reducing symptoms and improving health-related quality of life (HRQoL) and physical functions of patients with fibromyalgia and compared the effects of two different interdisciplinary treatment approaches. We conducted a prospective, randomized, controlled trial involving 66 women with fibromyalgia eligible for the study at a university hospital setting. The patients were randomized into three groups (allocation ratio 1:1:1) using a computer-generated random numbers: a long-term interdisciplinary treatment group (LG, n = 22) that participated in 10 sessions (3-h once-weekly session for 10 weeks) of cognitive behavioral therapy (CBT) together with exercise training and other fibromyalgia related educational programs (two full days); a short-term interdisciplinary treatment group (SG, n = 22) that received two full days of educational, exercise, and CBT programs; and a control group (CG, n = 22). The patients were evaluated at baseline and 6 months after treatment using the visual analog scale (pain, fatigue, and sleep), Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Short Form-36, tender point numbers, and pressure algometry as primary outcomes. The statistical analysis was confined to the ‘per-protocol’ set. No blinding was performed. The number of patients analyzed was 21 in the LG, 19 in the SG, and 19 in the CG. The intensity of pain (p < 0.001), severity of fatigue (p = 0.048), number of tender points (p = 0.002), and pressure pain threshold (p = 0.012) decreased significantly in both the LG and SG groups compared with controls. Moreover, physical functions (p = 0.017) and physical components of the HRQoL (p = 0.036) improved significantly in the intervention groups compared with the controls. However, there was no significant difference between intervention groups and the control group at the end of study in terms of quality of sleep (p = 0.055), severity of depressive symptoms (p = 0.696), and mental components of the HRQoL (p = 0.229). Finally, with the exception of the severity of fatigue and physical components of the HRQoL, there was no obvious significant difference between the efficacies of the two treatment approaches when compared with controls; the long-term treatment was found more effective in reducing pain than the short-term. Both, long- and short-term interdisciplinary treatments were effective in reducing the severity of some symptoms and disease activity in patients with fibromyalgia. The short-term program well meets the needs of women with fibromyalgia particularly in relation to pain and health status as measured using FIQ; however, a long-term program may be beneficial in reducing fatigue and improving physical function to a higher extent.     

Clinical relevance of P-glycoprotein activity on peripheral blood mononuclear cells and polymorphonuclear neutrophils to methotrexate in systemic lupus erythematosus patients

To elucidate the relationship between P-glycoprotein activity on peripheral blood leukocytes of systemic lupus erythematosus (SLE) patients with lupus arthritis and the clinical response to methotrexate. An observational study was made in patients with SLE according to ACR criteria 1997 who had arthralgia and arthritis and received methotrexate for ≥3 months. Methotrexate responders and non-responders were compared according to the Clinical Disease Activity Index. Mononuclear cells and polymorphonuclear neutrophils were isolated from SLE patients and P-glycoprotein expression was measured using the relative fluorescence index and percentage of positive cells. The chi-square test was used to compare P-glycoprotein activity between responders and non-responders. Thirty-two patients with a mean age of 45.4 ± 10.7 years were included: 34.4% had a response to methotrexate and 65.6% did not. Mean relative fluorescence units of both mononuclear cells and polymorphonuclear neutrophils were significantly lower in patients with a good response (7.0 ± 4.3 vs. 9.6 ± 3.8; p = 0.041 and 4.2 ± 3.5 vs. 7.6 ± 4.0; p = 0.004). The prevalence of low fluorescence levels (<6 relative fluorescence units), signifying higher P-glycoprotein activity of both mononuclear cells and polymorphonuclear neutrophils, was higher in methotrexate responders than in non-responders (27.3 vs. 4.8%; p = 0.10 and 81.8 vs. 23.8%; p = 0.003, respectively). In SLE patients with joint involvement treated with methotrexate, P-glycoprotein activity was higher in responders to methotrexate than in non-responders. Further studies are required to determine the mechanisms behind this finding and whether P-glycoprotein activity mediates alterations in methotrexate efficacy.